Ongoing research focuses on the exploration of pathologic inflammatory responses to acute respiratory virus infection and the use of this information to develop creative strategies to circumvent the lethal sequelae characteristic of this disease. In FY 2019, we contributed one (1) original research manuscript on this topic as follows: Manuscript #1: Title: Critical Adverse Impact of IL-6 in Acute Pneumovirus Infection. Severe respiratory virus infections feature robust local host responses that contribute to disease severity. Immunomodulatory strategies that limit virus-induced inflammation may be of critical importance, notably in the absence of antiviral vaccines. In this study, we examined the role of the pleiotropic cytokine IL-6 in acute infection with pneumonia virus of mice (PVM), a natural rodent pathogen that is related to respiratory syncytial virus and that generates local inflammation as a feature of severe infection. In contrast to Influenza A, PVM is substantially less lethal in IL-6 gene-deleted mice than it is in wild-type, a finding associated with diminished neutrophil recruitment and reduced fluid accumulation in lung tissue. Ly6C-hi proinflammatory monocytes are recruited in response to PVM via a CCR2-dependent mechanism, but they are not a major source of IL-6 nor do they contribute to lethal sequelae of infection. By contrast, alveolar macrophages are readily infected with PVM in vivo; ablation of alveolar macrophages results in prolonged survival in association with a reduction in virus-induced IL-6. Finally, as shown previously, administration of immunobiotic Lactobacillus plantarum to the respiratory tracts of PVM-infected mice promoted survival in association with diminished levels of IL-6. We demonstrated in this study that IL-6 suppression is a critical feature of the protective mechanism; PVM-infected IL-6 gene-deleted mice responded to low doses of L. plantarum, and administration of IL-6 overcame L. plantarum-mediated protection in PVM-infected wild-type mice. Critical point: As a whole, our findings connect the actions of IL-6 to PVM pathogenesis and suggest cytokine blockade as a feasible therapeutic modality in severe infection. Ref: Percopo CM, Ma M, Brenner TA, Krumholz JO, Break TJ, Laky K, Rosenberg HF. 2019. J Immunol. 2019. 202:871-882